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The killer immunoglobulin-like receptor KIR3DL1 in combination with HLA-Bw4 is protective against multiple sclerosis in African Americans

Genes & Immunity volume 17, pages 199–202 (2016)Cite this article

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Abstract

We investigated the role of the KIR loci and their HLA class I ligands in a large cohort of African American multiple sclerosis (MS) patients (N=907) and controls (N=1456). No significant differences in carrier frequencies for any KIR locus or haplotype were observed between cases and controls. However, examination of KIR in the context of their cognate HLA ligands revealed a strong protective effect for KIR3DL1 in combination with HLA-A and -B alleles bearing the Bw4 motif (P=10−8; odds ratio (OR)=0.60, confidence interval (CI)=0.50–0.71) and the Bw4 ligand alone (P<10−6; OR=0.63, CI=0.53–0.75). The observed effect cannot be explained by either a specific HLA-B allele or by linkage disequilibrium with HLA-DRB1 or HLA-A. The protective effect was observed only in individuals who were not positive for the MS risk allele HLA-DRB1*15:01 (P<10−6; OR=0.61, CI=0.51–0.74). Our study, the first investigation of KIR and MS in African Americans, confirms and refines previous findings in a European cohort.

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Acknowledgements

The authors thank the multiple sclerosis patients and healthy controls who participated in this study. We also thank Nezih Cereb and Soo Young Yang at Histogenetics Inc., and Hanne Harbo for useful discussion. This study was supported by grants from the National Institute of Health (R01NS046297 and U19NS095774). Recruitment of study participants and sample acquisition was supported by the National Multiple Sclerosis Society (RG2899-D11).

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Authors and Affiliations

  1. Department of Neurology, University of California, San Francisco, CA, USA

    J A Hollenbach, S J Caillier, P-A Gourraud & J R Oksenberg

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic in Arizona, AZ, USA

    M J Pando

  3. ATIP-Avenir Inserm Unit 1064, Hospital and University of Nantes, Nantes, France

    P-A Gourraud

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  1. J A Hollenbach
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Correspondence to J A Hollenbach.

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Hollenbach, J., Pando, M., Caillier, S. et al. The killer immunoglobulin-like receptor KIR3DL1 in combination with HLA-Bw4 is protective against multiple sclerosis in African Americans. Genes Immun 17, 199–202 (2016). https://doi.org/10.1038/gene.2016.5

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